Cancer is a group of diseases characterized by uncontrolled growth and spread of abnormal cells, and represents the second leading cause of death in the United States. Identifying new chemotherapeutic agents and characterizing mechanisms of drug resistance may improve treatment. The transcription factor NF-kB plays a major role in the regulation of genes which promote cancer cell proliferation and metastasis. NF-kB is activated by ionizing radiation, chemotherapeutic agents and tumor necrosis factor [TNF] a. Inhibition of NF-kB prevents tumor cell growth in vitro and in vivo. Therefore, inhibition of NF-kB is a novel approach to anti-cancer drug development. Signal pharmaceuticals, Inc. intends to develop therapeutics for treatment of cancer utilizing its expertise in intracellular signal transduction and gene expression. We aim to inhibit tumor growth and metastasis by modulating the expression of NF-kB-regulated genes. Two related projects will be initiated. The first seeks to identify inhibitors of key enzymes in the NF-kB activation pathway. Our goal is to develop high throughput, automated biochemical assays capable of identifying selective inhibitors of these enzymes. The second project will develop cell-based assays for the evaluation of NF-kB Inhibitors on tumor cell growth and migration. PROPOSED COMMERCIAL APPLICATION: Development of biochemical and cell-based as says to identify selective inhibitors of IkB kinases that inhibit tumor cell proliferation and migration. Use of these compounds to develop drugs for the treatment of cancer.